It involves complementary and inflammatory system proteins

It involves complementary and inflammatory system proteins, mast cells, eosinophils, basophils, macrophages, natural killer (NK) cells and cytokines [1]. Innate immunity, not only include cells, but also barriers that defend the organism to the penetration of pathogenic agents [2]. Important mediators of general inflammation are leukotrienes (LTs), formed from arachidonic Allopurinol [3]. The responsible enzyme for the arachidonic acid pathway and therefore the biosynthesis of such mediators is the 5-lipoxygenase [4], [5]. Recent studies have highlighted the involvement of the 5-lipoxygenase pathway both in the appearance and progression of many allergic disorders including asthma and in diverse inflammatory-associated diseases such as cardiovascular disease or rheumatoid arthritis [4]. Asthma is considered the 14th most significant chronic disease in the world considering its prevalence, extent and duration of the episodes. In this regard, it has been suggested that asthma affects around 315 million people worldwide, and within these about 10% present severe or uncontrolled asthmatic episodes [6], [7] and 250,000 annual deaths. These same studies estimate that the prevalence of asthma will continue to grow, affecting another 100 million people in 2025 [6]. Asthma can be defined as a chronic and highly heterogeneous inflammatory lung disorder characterized by recurrent episodes of reversible airflow obstruction, airway inflammation, bronchial hyperreactivity, as well as coughing, wheezing, dyspnea and chest tightness. In asthmatic patients is also frequent the occurrence of gastroesophageal reflux (GER) disease that can contribute to cough, bronchoconstriction and airway inflammation [7], [8], [9], [10]. In recent years, it has been reported that some mediators associated with inflammatory processes induce long-term functional modifications in the sensory airway neural pathways in rodent and primate asthma models [11]. The inflammatory mediators of asthma include cytokines, growth factors (peptide mediators), sensory neuropeptides and eicosanoids, end-products of arachidonic acid metabolism and include leukotrienes (LTs), prostaglandins (PGs) and thromboxane. These eicosanoids are becoming increasingly recognized as key mediators in the mechanisms underlying the inflammatory response associated to asthma [1], [2], [11], [12]. As greater appreciation for the inflammatory process in asthma has been realized, new treatments that inhibit specific steps within the inflammatory process have been undergoing clinical development, with particular attention to the involvement of the 5-lipoxygenase metabolic pathway in the pathogenesis of asthma [12].
Conclusion
Introduction
Design strategies for FLAP inhibitors and novel developments Since targeting the LT pathway has already proved efficacious with the successful application of oral CysLT receptor antagonists, researchers has shown great interest in the idea that FLAP inhibitors, drugs that intervene directly with LT formation, might have a great therapeutic potential for diseases which require anti-LT therapy (see recent reviews [4], [37], [38]).
Clinical significance of FLAP inhibitors in the LT pathway LTs are immune-modulating and proinflammatory lipid mediators, produced by variety of cell types including neutrophils, monocytes, macrophages, eosinophils, basophils, and mast cells [89], [90]. LTs are shown to play crucial roles in inflammatory and autoimmune disorders such as rheumatoid arthritis, inflammatory bowel disease, dermatomyositis, systemic sclerosis and multiple sclerosis [91], [92], [93]. The pathophysiological roles of LTs were also demonstrated for allergic disorders such as allergic rhinitis, allergic dermatitis and asthma as well as for other respiratory diseases like chronic obstructive pulmonary disease [94], [95]. LTs have also been implicated in several aspects of carcinogenesis by modulating tumor cell proliferation, differentiation, apoptosis as well as metastasis [5].